Searching for improved mimetic peptides inhibitors preventing conformational transition of amyloid-β42 monomer

A series of novel mimetic peptides were designed, synthesised and biologically evaluated as inhibitors of Aβ42 aggregation. One of the synthesised peptidic compounds, termed compound 7 modulated Aβ42 aggregation as demonstrated by thioflavin T fluorescence, acting also as an inhibitor of the cytotox...

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Bibliographic Details
Main Authors: Gera János
Szögi Titanilla
Bozsó Zsolt
Fülöp Lívia
Barrera Exequiel E.
Rodriguez Ana M.
Méndez Luciana
Delpiccolo Carina M.L
Mata Ernesto G.
Cioffi Federica
Broersen Kerensa
Paragi Gábor
Enriz Ricardo D.
Format: Article
Published: 2018
Series:BIOORGANIC CHEMISTRY 81
doi:10.1016/j.bioorg.2018.08.018

mtmt:3405755
Online Access:http://publicatio.bibl.u-szeged.hu/14901
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520 3 |a A series of novel mimetic peptides were designed, synthesised and biologically evaluated as inhibitors of Aβ42 aggregation. One of the synthesised peptidic compounds, termed compound 7 modulated Aβ42 aggregation as demonstrated by thioflavin T fluorescence, acting also as an inhibitor of the cytotoxicity exerted by Aβ42 aggregates. The early stage interaction between compound 7 and the Aβ42 monomer was investigated by replica exchange molecular dynamics (REMD) simulations and docking studies. Our theoretical results revealed that compound 7 can elongate the helical conformation state of an early stage Aβ42 monomer and it helps preventing the formation of β-sheet structures by interacting with key residues in the central hydrophobic cluster (CHC). This strategy where early “on-pathway” events are monitored by small molecules will help the development of new therapeutic strategies for Alzheimer’s disease. 
700 0 1 |a Szögi Titanilla  |e aut 
700 0 1 |a Bozsó Zsolt  |e aut 
700 0 1 |a Fülöp Lívia  |e aut 
700 0 1 |a Barrera Exequiel E.  |e aut 
700 0 1 |a Rodriguez Ana M.  |e aut 
700 0 1 |a Méndez Luciana  |e aut 
700 0 1 |a Delpiccolo Carina M.L.  |e aut 
700 0 1 |a Mata Ernesto G.  |e aut 
700 0 1 |a Cioffi Federica  |e aut 
700 0 1 |a Broersen Kerensa  |e aut 
700 0 1 |a Paragi Gábor  |e aut 
700 0 1 |a Enriz Ricardo D.  |e aut 
856 4 0 |u http://publicatio.bibl.u-szeged.hu/14901/1/BiorgChem-Elsevier.pdf  |z Dokumentum-elérés